Professor Brian Carr was born in Glasgow, Scotland in 1944 and grew up in London.

He graduated medical school at the University of London in 1967 and worked for several years in medicine and then in medical oncology. He realized that medical oncology was confusing and mainly witchcraft and decided to learn how to do research and was apprenticed at the Imperial Cancer Research Labs, London with Renato Dulbecco. After his molecular biology PhD (5′-mRNA capped ends) he moved after his advisor’s Nobel Prize with him to the USA.

He then repeated a solid tumor clinical Fellowship and simultaneous Post-Doc in chemical hepatocarcinogenesis at the McArdle Labs, Madison, WI. His first staff job was for 10 yr at the City of Hope, LA, first as Assistant and then as Associate Professor of Medicine, continuing to work on rodent hepatocarcinogenesis, with special interest in natural growth inhibitors (TGF beta).

He was then invited to set up the first liver cancer (HCC) group within the Liver Transplant Institute in Pittsburgh and was appointed as full Professor with tenure and worked there for 20 yr, both running the clinical HCC service and his lab working on HCC growth regulation.

His clinical interests have been for a long time in developing new HCC therapies, focussing initially on hepatic chemoembolization and subsequently on Yttrium-90 bead hepatic internal radioembolization and more recently on vitamin K as HCC therapy. Currently, he is analyzing HCC databases involving several thousand patients, to identify HCC phenotypes with differing clinical parameter patterns and prognoses. The main findings are that context is key, and that any given parameter (such as serum bilirubin or tumor mass) can only be understood in its total clinical context.

Scientifically, he spent several yr working on K vitamins, since their aberrant use is a key biochemical characteristic of HCC and helps identify one of the most important HCC tumor markers, DCP or des-gamma-carboxy prothrombin. DCP positive and AFP positive tumor cells have quite different regulation, just as AFP positive and AFP negative HCCs have differing phenotypes and prognosis. Vitamin K1 mediates inhibitory phosphorylation of Raf via PKC. Sorafenib is an FDA-approved HCC multikinase inhibitor working through direct Raf inhibition. Thus, vitamin K enhances Sorafenib-mediated Raf inhibition and thus enhances the HCC cell growth inhibition.

The clinical observations of HCC context, have led to the recent observations that blood platelet levels identify phenotypically different HCC patient subsets. This has been developed further by recently examining the actions of platelet lysates as promoters of HCC growth and invasion. This has been shown to be due in large part to platelet content of epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1). These factors also modulate HCC growth sensitivity and resistance to multikinase inhibitors. Therefore, the net effect of these therapies depends in part on the tumor (HCC) microenvironment. Thus, clinical observations led to experimental mechanistic observations, that in turn have led to clinical application: translational work.
He has published 296 papers-mainly on HCC and 4 books, 3 of which are on HCC and one on Psychological Aspects of Cancer and has written the chapter on Liver Tumors for the last 3 editions of: Harrison’s Principles of Internal Medicine (19th edition, April 2015).

Contact Information: brianicarr@hotmail.com